This protocol utilizes a dose intense chemotherapy treatment regimen which takes advantage of the synergistic activity between inhibitors of topoisomerase I and II. This is a phase I/II clinical trial for patients with advanced non-small cell lung cancer who have not received prior chemotherapy. We hypothesize that topotecan will be most effective in patients whose tumors exhibit high pretreatment levels of topoisomerase I. It is also hypothesized that topotecan treatment will result in a diminution of topoisomerase I levels and an elevation of topoisomerase II levels above baseline. The objectives are to 1) determine the response rate and duration of response, 2) observe the toxicity associated with this regimen, 3) to observe the effect in tumor biopsy samples, 4) to determine topotecan pharmacokinetic parameters and to correlate serum levels with toxicity and response to treatment and 5) to observe whether the activity of topoisomerase I and/or the extent of in vitro inhibition of topoisomerase I activity by topotecan in primary and metastatic non-small cell lung cancer correlate with clinical response to treatment with a topotecan-containing chemotherapy regimen. Nineteen patients were enrolled with only one partial response, one stable disease, 13 developed progressive disease, 4 were not evaluable. This trail was closed based upon review of patient response data in compliance with the "early stopping rule" as provided in the statistical section of the protocol.